Saturday, 1 January 2011

Want to know your disease risk? Check your exposome

reposted from:

crabsallover highlights, key points, comments or links.

Exposome (wikipedia)

WHEN it comes to health, which is more important, nature or nurture? You may well think your genes are a more important predictor of health and ill health. Not so fast. In fact, it transpires that our everyday environment outweighs our genetics, big time, when it comes to measuring our risk of disease. The genome is out - welcome the exposome.
"The exposome represents everything a person is exposed to in the environment, that's not in the genes," says Stephen Rappaport, environmental health scientist at the University of California, Berkeley. That includes stress, diet, lifestyle choices, recreational and medicinal drug use and infections, to name a few. "The big difference is that the exposome changes throughout life as our bodies, diets and lifestyles change," he says.
While our understanding of the human genome has been growing at an exponential rate over the last decade, it is not as helpful as we hoped in predicting diseases. "Genes only contribute 10 per cent of the overall disease burden," says Rappaport.
"Knowing genetic risk factors can prove absolutely useless," says Jeremy Nicholson at Imperial College London. He points to work by Nina Paynter at the Brigham and Women's Hospital in Boston, who investigated the effects of 101 genetic markers implicated in heart disease. After following over 19,000 women for 12 years, she found these markers were not able to predict anything about the incidence of heart disease in this group (The Journal of the American Medical Association DOI: 10.1001/jama.2010.119).
On the other hand, the impact of environmental influences is still largely a mystery. "There's an imbalance between our ability to investigate the genome and the environment," says Chris Wild, director of the International Agency for Research on Cancer, who came up with the idea of the exposome.
In reality, most diseases are probably caused by a combination of the two, which is where the exposome comes in. "The idea is to have a comprehensive analysis of a person's full exposure history," says Wild. He hopes a better understanding of exposures will shed a brighter light on disease risk factors.
There are likely to be critical periods of exposure in development. For example, the time from birth to 3 years of age is thought to be particularly important. "We know that this is the time when brain connections are made, and that if you are obese by this age, you'll have problems as an adult," says Nicholson.
In theory, a blood or urine sample taken from an individual could provide a snapshot of what that person has been exposed to. But how do you work out what fingerprints chemicals might leave in the body?
A blood or urine sample could provide a snapshot of what someone has been exposed to
The task is not as formidable as it sounds. For a start, researchers could make use of swathes of biobank information that has already been collected. "There has been a huge international funding effort in adult cohorts like the UK Biobank already," says Wild. "If we improved analysis, we could apply it to these groups."
Several teams are also working towards developing wearable devices to measure personal exposure to chemicals in the environment, for example(see "Bugging your biosphere").
Wearable devices to measure personal exposure to chemicals will soon be available
"We can put chemicals in categories," says Rappaport. "We could start by prioritising toxic chemicals, and look for markers of these toxins in the blood, while hormones and metals can be measured directly."
Rappaport is looking at albumin, a common protein in the blood that transports toxins to the liver where they are processed and broken down. He wants to know how it reacts with a range of chemicals, and is measuring the products. "You can get a fingerprint - a display of all the products an individual has been exposed to."
By combining this information with an enhanced understanding of how exposure affects health, the exposome could help better predict a person's true disease risk. And we shouldn't have to wait long - Rappaport reckons we can reap the benefits within a generation.
To this end, the US National Institutes of Health has set up an exposure biology programme. "We're looking for interactions between genes and exposure to work out an individual's risk of disease," says David Balshaw, who manages the programme. "It would allow you to tailor the therapeutic response to that person's risk."
An understanding of this interaction, reflected in a person's metabolic profile, might also help predict how they will respond to a drug. Nicholson has been looking for clues in metabolite profiles of urine samples.
Last year, his research group used these profiles to predict how individuals would metabolise paracetamol. "It turned out that gut microbes were very important," says Nicholson. "We've shown that the pre-dose urinary metabolite profile could predict the metabolism of analgesic drugs, and therefore predict drug toxicity." The findings suggest that metabolic profiles of exposure could help doctors tailor therapies and enable them to prescribe personalised medicines.
Justin Stebbing at Imperial College London has already shown that metabolic profiles of women with breast cancer can predict who will respond to certain therapies. It is early days, but the initial findings look promising.
"We're reaching the point where we're capable of assessing the exposome," says Balshaw. With the implications for understanding disease causes and risks, and a real prospect of developing personalised medicine, the exposome is showing more promise than the genome already, he adds.

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